Abstract
The current problem of increasing antibiotic resistance and the resurgence of numerous infections indicate the need for novel vaccination strategies more than ever. In vaccine development, the search for and the selection of adequate vaccine antigens is the first important step. In recent years, bacterial outer membrane proteins have become of major interest, as they are the main proteins interacting with the extracellular environment. Trimeric autotransporter adhesins (TAAs) are important virulence factors in many Gram-negative bacteria, are localised on the bacterial surface, and mediate the first adherence to host cells in the course of infection. One example is the Neisseria adhesin A (NadA), which is currently used as a subunit in a licensed vaccine against Neisseria meningitidis. Other TAAs that seem promising vaccine candidates are the Acinetobacter trimeric autotransporter (Ata), the Haemophilus influenzae adhesin (Hia), and TAAs of the genus Bartonella. Here, we review the suitability of various TAAs as vaccine candidates.
Highlights
Vaccination against human pathogens was first introduced in medicine in 1796 by Edward Jenner (Fig. 1)
We focus on the immunogenicity and vaccine candidacy of trimeric autotransporter adhesins (TAA) as one particular group of outer membrane proteins (OMPs) of Gram-negative bacteria [12–17]
Recombinant vaccine antigens, such as TAAs, that can be added on outer membrane vesicles (OMV), are primarily selected via reverse vaccinology, which includes in silico genome screening for open reading frames that likely encode for antigenic OMPs [53–55]
Summary
Vaccination against human pathogens was first introduced in medicine in 1796 by Edward Jenner (Fig. 1). A more recent vaccine delivery platform is the use of outer membrane vesicles (OMV) because of their high immunogenicity and virulence during infection [42, 51–53] Recombinant vaccine antigens, such as TAAs, that can be added on OMVs, are primarily selected via reverse vaccinology, which includes in silico genome screening for open reading frames that likely encode for antigenic OMPs [53–55]. New screening approaches for the development of vaccine candidates are still necessary, for instance, in vivo signature-tagged mutagenesis to target genes for novel virulence factors [79] or the use of reverse vaccinology to screen for antigenic OMPs. The immunodominant YadA of Y. enterocolitica has a monomeric molecular weight of approximately 47 kDa [31, 38] and the yadA gene is located on the 64-75 kb Yersinia virulence plasmid (pYV) [80, 81].
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